A major factor in the ability of the aging individual to continue independent activity is the status of his neuromuscular system. Muscle "atrophy" and loss of functional activity are well known aspects of aging in man. The underlying mechanism of this phenomenon is complex, involving possible genetic pre-programming, changes at various levels of the neuromuscular unit including the motor neuron, peripheral axon, motor endplate and the skeletal muscle, as well as age changes that may occur in various systems including vascular, hormonal, etc. Although skeletal muscle regeneration is active in the earlier decades of human life, it is both more extensive in rodents, in which whole muscles may regenerate, and continues throughout life. In the proposed investigation, we will take advantage of the fact that satellite cells capable of regenerating entire muscles persist as resting cells in the rodent muscle during the entire life of the animal. These may be called into activity by experimental muscle injury. The influence of aging on the regenerative capability of these cells will be investigated by the technique of explanting breis of minced muscle in suitable recipients, a well established method to "turn on" the regenerative process. The capability of aged satellite cell nuclei to regenerate new muscles in syngeneic young adult mice will be tested and the reverse experiment of causing "young" muscles to regenerate in old animals will be investigated. Morphologic criteria for regeneration will be assessed by light and electron microscopy and the protein synthetic capability of the regenerated muscle will be studied by biochemical methods. Initially the criterion for functional regeneration will be the restoration of normal limb movement. We hope to answer the question as to what aspect of aging alters regenerative capability, i.e. whether the resting satellite cells have lost their regenerative ability with time or whether factors derived from the host animal prevent the satellite cell from being "turned on". A better understanding of the regulation of the maintenance and repair of muscle cells has significant implications for understanding of the motor unit in aged individuals and those who suffer from neuromuscular disease.